Structure of 19181-64-7
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 19181-64-7 |
Formula : | C9H8N2O2 |
M.W : | 176.17 |
SMILES Code : | OC1=C2C=C(OC)C=CC2=NC=N1 |
MDL No. : | MFCD06657614 |
InChI Key : | NOFVNLZQAOGUIT-UHFFFAOYSA-N |
Pubchem ID : | 135451423 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.11 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 48.05 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.24 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.86 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.91 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.34 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.8 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.42 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.27 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.01 |
Solubility | 1.73 mg/ml ; 0.0098 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.66 |
Solubility | 3.89 mg/ml ; 0.0221 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.88 |
Solubility | 0.233 mg/ml ; 0.00132 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.73 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.52 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With 8-quinolinol; sodium hydroxide; copper dichloride In water at 20℃; for 0.333333 h; Sealed tube; Microwave irradiation | General procedure: In a 10 mL glass tube 2-iodobenzoic acid (1.0 mmol), acetamidine hydrochloride (1.2 mmol), CuCl2 (0.1 mmol), L2 (0.1 mmol), and NaOH (4.0 equiv.) and 3.0 mL water were placed. The vessel was then sealed with a septum and placed into the microwave cavity. Initial microwave irradiation of 120 W by using a CEM Discover microwave synthesizer was used at the room temperature for 20 min. The reaction mixture was stirred continuously during the reaction. After completion of the reaction, the solvent was removed in vacuo. The residue was purified by silica gel column chromatography to afford the corresponding product. All the products were confirmed by NMR and MS spectroscopic analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With ytterbium(III) triflate In 1,3,5-trimethyl-benzene at 165℃; for 6 h; Inert atmosphere | General procedure: A mixture of 2-aminobenzamide (1, 4.0 mmol), carboxamide (2, 6.0 mmol), Yb(OTf)3 (0.20 mmol,5.0 molpercent), and mesitylene (5.0 mL) was placed in a 20-mL Pyrex flask equipped with a magnetic stirring bar and a reflux condenser under a flow of argon. The reaction was carried out at 120-165 oC (bath temp.) for 6 h with stirring. Then, the reaction mixture was cooled to room temperature, and analyzed by GLC, GC-MS (EI), and LC-MS (ESI). After evaporation of mesitylene under vacuum,the products (3) were isolated by recrystallization from MeOH/hexane and/or medium pressure column chromatography on silica gel (eluent: EtOAc/hexane = 50/50 ~ EtOAc 100percent. For 3j, eluent:MeOH/CHCl3 = 50/50). 1H NMR spectra were recorded at 400 MHz, and 13C NMR spectra wererecorded at 100 MHz in DMSO-d6. The analytical and spectral data of 3a-e,38 3f,39 3g,40 3h,41 and3j,42 were consistent with those reported previously. The product, 3i, was characterized below. |
50% | at 160℃; for 0.333333 h; Microwave irradiation | Example30: (4-Chloro-phenyl)-{4-[(3S,4S)-4-hydroxy-l-(6-methoxy-quinazolin-4yl)- pyrrolidin-3-yl]-piperazin-l-yl}-methanone[00243] Step 1. 6-Methoxy-3H-quinazolin-4-one[00244] To 1.025 mmoles of 2-amino-5-methoxy anthranilic acid add 6.14 mmoles of formamide and microwave reaction mixture for 20mins at 1600C. After cooling the solid was diluted with 1OmL ethanol, the mixture was heated to reflux and allowed to cool slowly. The solid obtained was filtered and washed with cold ethanol and vaccum dried to give the title compound in 50percent yield.[00245] LC-MS: m/z = 177 (M+ +1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | at 125℃; for 18 h; | [0144] A mixture of 2-amino-5-methoxybenzoic acid (10.0 g, 59.9 mmol), formamidine acetate (12.3 g, 119 mmol) in 80 mL of 2-methoxyethanol was heated at 125 °C for 18 hours. After being cooled to room temperature, the precipitate was collected by filtration, washed twice with 2-methoxyethanol and dried in the vacuum to provide 6-methoxyquinazolin- 4(3H)-one (9.1 g, 87percent yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | at 130℃; for 2 h; Inert atmosphere; Microwave irradiation | 5-methoxybenzamide (83 mg, 0.5 mmol), [Cp * Ir (2,2'-bpyO) (H2O)](5.4 mg, 0.005 mmol, 1 molpercent), cesium carbonate (49 mg, 0.15 mmol, 0.3 equiv.) And methanolInto a dry 5mL microwave reaction tube. Nitrogen protection in microwave tube placed in a single mode pressure microwave synthesizerCEM, USA). After the reaction mixture was reacted at 130 ° C for 2 hours, it was cooled to room temperature. Solvent was removed by rotary evaporation and then passedColumn chromatography (developing solvent: petroleum ether / ethyl acetate) gave the pure target compound in a yield of 91percent |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With 8-quinolinol; sodium hydroxide; copper dichloride In water at 20℃; for 0.333333 h; Sealed tube; Microwave irradiation | General procedure: In a 10 mL glass tube 2-iodobenzoic acid (1.0 mmol), acetamidine hydrochloride (1.2 mmol), CuCl2 (0.1 mmol), L2 (0.1 mmol), and NaOH (4.0 equiv.) and 3.0 mL water were placed. The vessel was then sealed with a septum and placed into the microwave cavity. Initial microwave irradiation of 120 W by using a CEM Discover microwave synthesizer was used at the room temperature for 20 min. The reaction mixture was stirred continuously during the reaction. After completion of the reaction, the solvent was removed in vacuo. The residue was purified by silica gel column chromatography to afford the corresponding product. All the products were confirmed by NMR and MS spectroscopic analysis. |
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